Hypertensive disorder of pregnancy, manifesting around the second half of pregnancy, affects 2 – 8% of global pregnancies, and this premature serious hypertension of pregnancy is equally dangerous for both the mother and child. PE is characterized by the occurrence of hypertension and proteinuria after 20 weeks of gestation. Although it is a leading cause of maternal and perinatal morbidity and mortality worldwide, it complicates 10–15% of all maternal cases and causes serious morbidity in neonates, such as preterm birth and low birth weights [1,2]. However, although much research has been conducted, little is currently known about the precise mechanisms underlying PE, thus limiting the development of effective early diagnostic and preventive strategies. Early detection of PE remains elusive, and there is an increased need for reliable biomarkers to predict PE before its clinical manifestation. The critical role of oxidative stress in PE pathophysiology and endothelial dysfunction, the hallmark of the disease, has provided increasing impetus to uncover such markers, which currently remain elusive [3, 4].

At present, PE is known to be a multifactorial disease comprising genetic, immunological, and environmental factors, but for all of these, abnormal placentation is a common theme [5]. Trophoblastic invasion (red arrow) remodels maternal spiral arteries to accommodate high-capacity blood flow to the placenta (blue arrow) during healthy pregnancy. However, this process is incomplete in PE and is associated with shallow trophoblastic invasion and restricted placental blood flow, which frequently causes intermittent hypoxic or reoxygenation events in the placenta [6]. These hypoxic conditions generate reactive oxygen species (ROS), leading to oxidative stress, damage to placental and vascular endothelial cells, and progression of hypertension and proteinuria associated with PE[7]. An imbalance between ROS production and the body’s defenses creates oxidative stress, which results in lipid peroxidation, DNA damage, and cellular dysfunction [8]. Because oxidative stress plays a central role in PE, MDA, a marker of oxidative damage, is also being evaluated for its validity as an early predictor of the disease [9].

Of the oxidative stress markers, MDA (the byproduct of lipid peroxidation) is often investigated as stable and easy to measure in the serum [10]. Studies have indicated extremely high levels of MDA in women with PE compared to normotensive pregnancies [11], demonstrating oxidative stress and cellular damage in PE. In addition, pre-eclamptic women are characterized by reduced total antioxidant capacity (TAC) and lower activity of superoxide dismutase (SOD) and other enzymes, which may contribute to diminished antioxidant defenses and persistence and progression of oxidative damage in these patients [12,13]. In addition to damaging the endothelium, this heightened oxidative state promotes the release of pro-inflammatory cytokines and anti-angiogenic factors, such as soluble fms like tyrosine kinase 1 (sFlt 1), which further impairs endothelial function and upsets the balance of angiogenic factors necessary for healthy placental development [14].

Currently, methods to predict PE are lacking, and present means for prediction are limited to maternal history and imaging techniques, both of which have low predictive value in early pregnancy, where interventions are most effective [15]. Accessible and reliable serum biomarkers, such as MDA and TAC, may aid the early detection of PE and serve as a basis for developing targeted interventions to prevent PE from occurring due to oxidative stress [16]. In the present study, we studied MDA and other oxidative stress markers in pre-eclamptic as compared to normotensive pregnancies in order to serve as possible early markers of PE and contribute to the development of improved diagnostic protocols and preventive measures for this high-risk condition [17].

Study Design

In this study, we compared oxidative stress markers in pregnant women with preeclampsia (PE) to normotensive pregnant controls using a cross-sectional design. This study aimed to identify oxidative stress biomarkers (malondialdehyde (MDA), total antioxidant capacity (TAC), and superoxide dismutase (SOD) levels) as reliable predictors of PE degradation. The study was conducted at a university-affiliated hospital, in which 150 pregnant women (stratified into two groups) who were clinically diagnosed were included.

Sample Selection

The study cohort comprised 75 pregnant women diagnosed with PE and 75 pregnant controls. Women with a clinical diagnosis of PE (defined as new-onset hypertension with proteinuria ≥ 0.3 g per 24 hours after 20 weeks of gestation) but no other pregnancy complications were included in the PE group; all were between 18 and 40 years old. Pregnant women with gestational age and body mass index (BMI) without any other medical conditions or normotension were selected as the control group. Patients with chronic hypertension, renal disease, diabetes, and pre-existing cardiovascular conditions were excluded.

Ethical Considerations

The institutional ethics review board approved the ethical principles, and all participants provided written informed consent. The purpose of the study, role of the participants, and confidentiality of the data were provided to the participants. They were also informed about their right to withdraw from the study at any time, with no impact on medical care.

Data Collection

Clinical and Demographic Data

A detailed assessment was performed for each participant after reviewing their medical and demographic information. The collected variables included age, gestational age, BMI, parity, and blood pressure measurements. The pre-eclamptic group was confirmed by proteinuria assessment using urine dipstick analysis.

Blood Sample Collection

All participants were asked to refrain from food for 12 hours prior to blood sample collection in the morning. Venous blood (approximately 10 mL) was drawn from each participant and placed in tubes with ethylenediaminetetraacetic acid (EDTA) to prevent coagulation. The serum was separated by centrifugation of the samples at 4 °C and 3000 rpm for 10 min and stored at -80 °C until biochemical analysis.

Laboratory Analysis

However, it is also possible to measure malondialdehyde (MDA) levels.

Lipid peroxidation was measured using the thiobarbituric acid reactive substance (TBARS) assay and MDA levels. MDA reacts with thiobarbituric acid (TBA) under acidic conditions to form a colorimetric complex that can be measured at 532 nm using this method. MDA was expressed as nmol/mL.

Thisis is also known atotal antioxidantncapacity (TAC).

An ELISA was used to measure TAC, a measure of the combined antioxidant effect in the serum of all components in the sample. The results are expressed as mM Trolox equivalents and higher antioxidant capacity.

Activity of Superoxide Dismutase (SOD)

Enzymatic antioxidant defenses were estimated by measuring SOD activity using a colorimetric assay that relies on inhibition of superoxide radical formation by the enzyme. Absorbance was read at 450 nm, and the results were presented as U per mL.

Statistical Analysis

Data were analyzed using SPSS software (version 25.0). Demographic and clinical variables were analyzed using descriptive statistics (mean ± standard deviation). For normally distributed measures, between-group comparisons were made using independent t-tests, and for variables with non-normal distributions, the Mann-Whitney U test was used. The relationship between the oxidative stress markers and PE severity was evaluated using Pearson’s correlation analysis.

Multivariate regression analysis was performed to adjust for potential confounders (including age, BMI, and gestational age). Statistical significance was defined as P < 0.05.

Limitations

The cross-sectional design of the study prevented us from making causative inferences, but it aimed to identify early PE biomarkers. Further longitudinal studies are needed to validate the prediction of PE onset. Moreover, owing to variations in TAC and SOD biochemical assays, such as laboratory conditions, standardization is required for the clinical application of this technique.

The study evaluated Oxidative stress markers, specifically malondialdehyde (MDA), total antioxidant capacity (TAC), and superoxide dismutase (SOD) activity, in women with preeclampsia (PE) compared to normotensive pregnant controls. The findings showed significant differences in these biomarkers between the two groups, supporting the hypothesis that oxidative stress is more pronounced in patients with PE.

Demographic and Clinical Characteristics

Table 1 summarizes the demographic and clinical data of the study participants. There were no statistically significant differences between the PE and control groups in terms of age, body mass index (BMI), and gestational age, ensuring that these variables did not confound biomarker analysis.

*Significant difference at P < 0.05.

Comparison of Oxidative Stress Markers

The concentrations of MDA, TAC, and SOD were compared between the PE and control groups (Table 2). MDA levels were significantly higher in the PE group (5.12 ± 1.43 nmol/mL) compared to controls (2.86 ± 1.01 nmol/mL, p < 0.01), indicating greater oxidative damage in PE. Conversely, TAC and SOD activities were significantly lower in the PE group, suggesting compromised antioxidant defenses.

*Significant difference at P < 0.05.

Graphical Representation of Biomarker Levels

Figures 1–3 graphically illustrate the differences in MDA, TAC, and SOD levels between the PE and control groups, highlighting the significant alterations in oxidative stress markers associated with PE.

Figure 1 shows that MDA levels were substantially higher in the PE group than in the control group, reinforcing the observation of increased oxidative stress in PE.

Figure 2 demonstrates that TAC levels were lower in the PE group, indicating reduced antioxidant capacity and weakened oxidative defence mechanisms in PE.

Figure 3 shows the SOD activity levels, where the PE group displayed significantly lower activity than the controls, further supporting impaired antioxidant enzyme function in PE.

Correlation Analysis

Correlation analysis was conducted to explore the relationship between oxidative stress markers and blood pressure levels in the PE group (Table 3). MDA levels were positively correlated with systolic blood pressure (r = 0.45, p < 0.01) and diastolic blood pressure (r = 0.42, p < 0.01), whereas TAC and SOD levels were inversely correlated with blood pressure measurements, suggesting that lower antioxidant capacity is associated with more severe hypertension in PE.

*Significant correlation at P < 0.05.

Summary of Findings

These results indicated that oxidative stress, as reflected by elevated MDA levels and reduced TAC and SOD activity, was significantly associated with PE. The positive correlation between MDA and blood pressure suggests that oxidative stress contributes to the severity of hypertension in PE. These findings support the potential utility of MDA, TAC, and SOD as biomarkers for early detection and monitoring of PE progression.

We evaluated oxidative stress markers (malondialdehyde, total antioxidant capacity, and superoxide dismutase activity) in women with preeclampsia compared to normotensive pregnant controls. The biomarkers in these results revealed major changes in these biomarkers in the PE group, providing more support for oxidative stress associated with PE pathogenesis. Increased lipid peroxidation, as indicated by elevated MDA levels, together with decreased TAC and SOD activity, also suggests that oxidative stress and impaired antioxidant defenses are essential for the clinical manifestations of PE.

The results were compared with those of previous research.

The findings of this study are in agreement with those of previous studies demonstrating that PE results in increased oxidative stress and antioxidant deficiency. Mammalian adipose tissues and marrow adipocytes exhibited increased levels of MDA in the PE group, supporting previous findings that identified lipid peroxidation as an essential factor in the disease [18]. For example, Hubel et al. reported similar increases in MDA in pre-eclamptic women [19] and linked them to endothelial dysfunction and the development of hypertension associated with PE. Our study also showed lower TAC and SOD activity in PE patients, in accordance with Wang et al. [20], who found less antioxidant capacity in women with PE and concluded that impaired oxidative defense mechanisms worsen cellular damage and endothelial dysfunction in the disorder.

In this regard, decreased SOD activity in the PE group is of particular significance because SOD is a prostate enzyme involved in neutralizing superoxide radicals, a major reactive oxygen species (ROS) associated with PE [21]. Other studies have documented lower SOD activity, indicating that with lesser enzymatic defense, oxidative stress might be elevated in PE [22]. In addition, these findings support the notion that oxidative stress is implicated in the etiology of PE, involving cellular damage and inflammation, which together cause the hypertensive state observed in PE.

The applications of the serious language game described in this paper have clinical implications in two areas.

The positive correlation between oxidative stress markers and blood pressure levels in patients with PE may indicate the possibility of using these biomarkers as markers of disease severity. In particular, the positive correlation between MDA levels and blood pressure suggests that [23]as PE progresses, oxidative damage may worsen, making MDA a potential marker of disease progression. In addition, the correlations between TAC, SOD activity, and blood pressure were negative, indicating that impaired antioxidant protection can cause an increase in hypertension, thus providing therapeutic target candidates.

These findings have significant clinical implications for the early diagnosis and prevention of PE. The use of MDA, TAC, and SOD activity as routine screening biomarkers during prenatal care allows the early detection of PE in at-risk populations. Early detection of PE is important because timely intervention strategies, such as antioxidant supplementation or lifestyle modifications, could ameliorate oxidative stress and reduce the occurrence of severe PE [24]. Although the therapy is somewhat inconsistent, studies have demonstrated that antioxidant therapies, such as vitamin C and E supplementation, provide some benefit in reducing oxidative stress and improving endothelial function in PE[25].

The limitations and future directions of this study are also discussed.

This study highlights the importance of oxidative stress in PE, but there are a few limitations that should be considered. These biomarkers represent promising candidates for subsequent prospective longitudinal studies to correlate changes with the onset of PE; however, their predictive power cannot be determined with certainty at this time because of the cross-sectional design. Furthermore, the variability of oxidative stress markers, TAC and SOD activity, was dependent on dietary and environmental factors, which were not observed in this study. Future studies should examine the influence of controlled antioxidant supplementation on TAC and SOD activity in relation to their role in the maintenance of oxidative stress in PE.

Moreover, the clinical applicability of these biomarkers must be validated across different populations. For example, studies examining whether antioxidant supplementation works would be helpful because many of the common regions for PE are in regions where there may be limited advanced healthcare. Additional oxidative stress markers, glutathione peroxidase and catalase, might also be used in research to better understand the oxidative mechanisms responsible for PE.

The results regarding MDA, TAC, and SOD activity support this hypothesis, as MDA is elevated and TAC and SOD activity are reduced in pre-eclamptic women, which supports the hypothesis that oxidative stress plays a central role in the pathogenesis of PE. This is consistent with existing research and adds to the growing body of evidence that oxidative stress markers can be useful early interventions for PE, and their use earlier could mean earlier diagnosis and intervention. Oxidative stress has become increasingly appreciated in the pathogenesis of PE, leading to the promise of future research and clinical trials on antioxidant therapies to improve maternal and fetal outcomes.

Evidence for the significant involvement of oxidative stress in the pathogenesis of pre-eclampsia (PE) provided by this study is supported by the documentation of elevated levels of malondialdehyde (MDA), decline in total antioxidant capacity (TAC), and superoxide dismutase (SOD) activity in women with PE compared to normotensive controls. The high correlation between MDA levels and blood pressure and the inverse relationship between TAC, SOD, and blood pressure indicate that oxidative stress plays a role in the severity and progression of PE. Biomarkers in these categories are promising early indicators for clinical use, empowering an ongoing, proactive monitoring, and care approach in high-risk pregnancies.

These results are consistent with previous research on oxidative damage and decreased antioxidant defenses in PE, and strengthen the rationale for antioxidant therapeutic interventions to attenuate oxidative stress and ameliorate maternal outcomes. These biomarkers could be incorporated into prenatal screening protocols for earlier diagnosis and custom interventions, which might lower the severity of PE complications in both mothers and infants. Further validation of these biomarkers and optimization of preventive interventions require future studies on the longitudinal outcomes and effectiveness of antioxidant therapies in PE. This research will help advance clinical practices in prenatal care by identifying promising biomarkers to manage PE.

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